Causes of Death after a Hospitalization with AKI.

Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.

Association Between High Environmental Heat and Risk of Acute Kidney Injury Among Older Adults in a Northern Climate: A Matched Case-Control Study.

BACKGROUND: An association between high heat and acute kidney injury (AKI) has been reported in warm climates. However, whether this association generalizes to a northern climate, with more variable temperatures, is unknown. STUDY DESIGN: Matched case-control study. SETTING & PARTICIPANTS: Our study focused on older adults (mean age, 80 years) in the northern climate of Ontario, Canada. 52,913 case patients who had a hospital encounter with AKI in April through September 2005 to 2012 were matched with 174,222 controls for exact date, age, sex, rural residence, income, and history of chronic kidney disease. PREDICTOR: Heat periods were defined as 3 consecutive days exceeding the 95th percentile of area-specific maximum temperature. OUTCOMES: Hospital encounter (inpatient admission or emergency department visit) with a diagnosis of AKI. MEASUREMENTS: ORs (95% CIs) were used to assess the association between heat periods and AKI. To quantify the effect in absolute terms, we multiplied the population incidence rate of AKI in the absence of heat periods by our adjusted OR (an approximate of relative risk). RESULTS: Heat periods were significantly associated with higher risk for AKI (adjusted OR, 1.11; 95% CI, 1.00-1.23). Heat periods in absolute terms were associated with an additional 182 cases of AKI per 100,000 person-years during the warm season. LIMITATIONS: We did not know how long persons were outside or if they had access to air conditioning. CONCLUSIONS: In a northern climate, periods of higher environmental heat were associated with a modestly higher risk for hospital encounter with AKI among older adults.

The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). Methods: We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD. Results: Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies). Conclusion: Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful.

Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES: Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 µmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. RESULTS: Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01082874.

The risk of perioperative bleeding in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Worldwide, millions of patients with chronic kidney disease undergo surgery each year. Although chronic kidney disease increases the risk of bleeding in nonoperative settings, the risk of perioperative bleeding is less clear. We conducted a systematic review and meta-analysis to summarize existing information and quantify the risk of perioperative bleeding from chronic kidney disease. METHODS: We screened 9376 citations from multiple databases for cohort studies published between 1990 and 2011. Studies that met our inclusion criteria included patients undergoing any major surgery, with a sample size of at least 100 patients with chronic kidney disease (as defined by the primary study authors with an elevated preoperative serum creatinine value or a low estimated glomerular filtration rate). Their outcomes had to be compared with a reference group of at least 100 patients without chronic kidney disease. Our primary outcomes were (1) receipt of perioperative blood transfusions and (2) need for reoperation for reasons of bleeding. RESULTS: Twenty-three studies met our criteria for review (20 cardiac surgery, 3 non-cardiac surgery). Chronic kidney disease was associated with a greater risk of requiring blood transfusion (7 studies in cardiac surgery, totaling 22,718 patients) and weighted incidence in patients with normal kidney function was 53% and in chronic kidney disease was 73%; pooled odds ratio, 2.7 (95% confidence interval, 2.1-3.4). After adjustment for relevant factors, the association remained statistically significant in 4 studies. Chronic kidney disease was associated with more reoperation for reasons of bleeding (14 studies in cardiac surgery, totaling 569,715 patients) and weighted incidence in patients with normal kidney function was 2.4% and in chronic kidney disease was 2.7%; pooled odds ratio, 1.6 (95% confidence interval, 1.3-1.8). However, after adjustment for relevant factors (as done in 5 studies), the association was no longer statistically significant. CONCLUSIONS: Chronic kidney disease is associated with perioperative bleeding but not bleeding that required reoperation. Further studies should stage chronic kidney disease with the modern system, better define bleeding outcomes, and guide intervention to improve the safety of surgery in this at-risk population.

Magnesium and Fracture Risk in the General Population and Patients Receiving Dialysis: A Narrative Review.

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

Justification: Le magnésium est un minéral essentiel pour le métabolisme osseux, mais on en sait peu sur la façon dont un apport en magnésium modifie le risque de fracture. Nous avons procédé à un examen narratif afin de mieux comprendre comment les maladies liées à la densité minérale osseuse et le risque de fracture sont affectés par un apport en magnésium (supplémentation, régime alimentaire ou modification de la concentration de dialysat de magnésium) chez les personnes atteintes d'insuffisance rénale. Sources: Essais cliniques et études observationnelles examinés par des pairs. Méthodologie: Nous avons répertorié les articles pertinents dans les bases de données MEDLINE et EMBASE. Une version modifiée des critères de contrôle de la qualité des études de Downs et Black a servi à évaluer la qualité méthodologique des essais cliniques retenus. Principaux résultats: Le rôle d'un apport en magnésium dans la prévention des fractures n'est pas clair, tant dans la population générale que chez les patients sous dialyse d'entretien. Chez les personnes ayant une fonction rénale normale, deux méta-analyses ont montré que les personnes dont le régime alimentaire est riche en magnésium présentent une densité minérale osseuse plus élevée; alors qu'une revue systématique n'a montré aucun effet sur le risque de fracture. Chez les patients sous hémodialyse d'entretien ou dialyse péritonéale, une concentration plus élevée de dialysat de magnésium est associée à une plus faible concentration d'hormone parathyroïdienne, mais on en sait peu sur les autres effets liés aux os. Dans deux études observationnelles portant sur des patients sous hémodialyse, une concentration plus élevée de magnésium sérique a été associée à un risque plus faible de fracture de la hanche. Limites: Cet examen narratif ne comprend que des articles rédigés en anglais. Il est possible que les effets d'un apport en magnésium observés dans la population générale ne puissent s'appliquer aux personnes atteintes d'une néphropathie chronique, en particulier aux personnes sous dialyse.

Predicting Myocardial Injury and Other Cardiac Complications After Elective Noncardiac Surgery with the Revised Cardiac Risk Index: The VISION Study.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is widely used to estimate risk of cardiac complications after noncardiac surgery; its estimates do not capture myocardial injury after noncardiac surgery (MINS). We evaluated the incidence of cardiac complications including MINS across RCRI risk classes and the RCRI's ability to discriminate, before surgery, between patients who will experience these complications and those who will not. METHODS: This was a secondary analysis of a prospective cohort study of 35,815 patients ≥ 45 years old who had elective inpatient noncardiac surgery from 2007 to 2013 at 28 centres in 14 countries. The primary outcome was a composite of MINS, myocardial infarction, nonfatal cardiac arrest, or cardiac death within 30 days after surgery. The secondary outcome was this composite without MINS. RESULTS: The primary outcome occurred in 4725 patients (13.2%); its incidences across RCRI classes I (no risk factors), II (1 risk factor), III (2 risk factors), and IV (≥ 3 risk factors) were, respectively, 8.2%, 15.4%, 26.6%, and 40.2% (C-statistic for discrimination 0.65 [95% confidence interval 0.62-0.68]). The secondary outcome occurred in 1174 patients (3.3%) with incidences of 1.6%, 4.0%, 7.9%, and 12.9%, respectively (C-statistic 0.69 [0.65-0.72]). Thirty-five percent of primary outcome events and 26.9% of secondary outcome events occurred in patients with no RCRI risk factors. CONCLUSION: The RCRI alone is not sufficient to guide postoperative cardiac monitoring because 1 in 12 patients ≥ 45 years of age without any RCRI risk factors have a cardiac complication after major noncardiac surgery, and most of them would be missed without systematic troponin testing.

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

PURPOSE OF REVIEW: Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps. SOURCES OF INFORMATION: Peer-reviewed articles. METHODS: We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist. KEY FINDINGS: The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia. LIMITATIONS: Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.

CONTEXTE MOTIVANT LA REVUE: Les stratégies visant à atténuer les crampes musculaires sont parmi les principales priorités de recherche des patients hémodialysés. L'hypomagnésémie étant un possible facteur de risque, nous avons procédé à une revue de la littérature afin de mieux en comprendre l'épidémiologie, et d'examiner la physiologie et l'épidémiologie des crampes musculaires. Nous souhaitions également examiner les données probantes issues d'études interventionnelles portant sur l'effet des thérapies à base de dialysat de magnésium et de magnésium oral sur les crampes musculaires. SOURCES: Articles examinés par les pairs. MÉTHODOLOGIE: Nous avons cherché les articles pertinents dans les principales bases de données bibliographiques, notamment MEDLINE et EMBASE. La qualité méthodologique a été évaluée à l'aide d'une version modifiée des critères de contrôle de la qualité des études de Downs et Black. PRINCIPAUX RÉSULTATS: L'étiologie des crampes musculaires chez les patients hémodialysés est mal comprise et il n'existe aucune stratégie de prévention ou traitement clairement fondé sur des données probantes. Plusieurs facteurs pourraient jouer un rôle, notamment de faibles concentrations sériques de magnésium. La prévalence de l'hypomagnésémie (concentration inférieure à 0,7 mmol/L) chez les patients hémodialysés variait de 10 à 20 %. Une faible consommation de magnésium dans l'alimentation, la prise de médicaments inhibant l'absorption du magnésium (ex. les inhibiteurs de la pompe à protons), l'excrétion accrue du magnésium (ex. dose élevée de diurétiques de l'anse) et une faible concentration de dialysat de magnésium figuraient parmi les causes d'hypomagnésémie. Un taux de dialysat de magnésium inférieur ou égal à 0,5 mmol/L pourrait être associé à une diminution de la concentration sérique de magnésium au fil du temps. Les résultats préliminaires de certaines études observationnelles et interventionnelles suggèrent qu'une concentration sérique plus élevée de magnésium dans le dialysat augmenterait les concentrations sériques de magnésium et pourrait réduire la fréquence et la sévérité des épisodes de crampes musculaires. La qualité des preuves appuyant ce bienfait est cependant limitée. Des essais multicentriques et à plus vaste échelle sont nécessaires pour juger si un traitement à base de magnésium peut véritablement réduire les crampes musculaires chez les patients hémodialysés. Dans les études menées jusqu'à maintenant, l'augmentation de la concentration de dialysat de magnésium semblait bien tolérée et a été associée à un faible risque d'hypermagnésémie symptomatique. LIMITES: Peu d'études interventionnelles ont examiné l'effet de la prise de magnésium sur les crampes musculaires des patients hémodialysés, et la plupart de celles-ci constituaient des plans pré- ou post-études non randomisées.

Cultivating Innovative Pragmatic Cluster-Randomized Registry Trials Embedded in Hemodialysis Care: Workshop Proceedings From 2018.

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials.

L'hémodialyse constitue un traitement essentiel au maintien de la vie pour les personnes atteintes d'insuffisance rénale. Les patients hémodialysés voient cependant leur qualité et leur espérance de vie réduites. Des données de recherches probantes, provenant de vastes essais cliniques contrôlés à répartition aléatoire, sont nécessaires pour améliorer l'expérience, les résultats et les soins des patients hémodialysés. Grâce au soutien des Instituts de recherche en santé du Canada (IRSC) et de leur Stratégie de recherche axée sur le patient (SRAP), l'initiative sur les essais cliniques novateurs (ECN) en centres d'hémodialyse a réuni divers intervenants en santé rénale (chercheurs, patients, fournisseurs de soins et administrateurs), du Canada et de partout dans le monde, lors d'un colloque qui s'est tenu à Toronto les 2 et 3 juin 2018. Ce colloque a permis d'accroître la sensibilisation et les connaissances sur la conduite d'essais cliniques novateurs, répartis en grappes, pragmatiques et intégrés aux soins d'hémodialyse de routine. Cette rencontre a également fourni une occasion de discuter de nouvelles idées d'essais cliniques et de susciter les appuis nécessaires à leur réalisation. Le colloque s'est déroulé sous forme de présentations structurées, de discussions animées en groupe et de rétroaction de la part d'un comité d'experts. Les idées de recherche prometteuses et les partenariats issus de ce colloque continueront d'être développés pour soutenir la réalisation d'essais cliniques futurs de grande envergure.